Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).

Outcomes of Vasopressin-Receptor Agonists Versus Norepinephrine in Adults With Perioperative Hypotension: A Systematic Review.

Consensus statements recommend the use of norepinephrine and/or vasopressin for hypotension in cardiac surgery. However, there is a paucity of data among other surgical subgroups and vasopressin analogs. Therefore, the authors conducted a systematic review of randomized controlled trials (RCTs) to compare vasopressin-receptor agonists with norepinephrine for hypotension among those undergoing surgery with general anesthesia. This review was registered prospectively (CRD42022316328). Literature searches were conducted by a medical librarian to November 28, 2023, across MEDLINE, EMBASE, CENTRAL, and Web of Science. The authors included RCTs enrolling adults (≥18 years of age) undergoing any surgery under general anesthesia who developed perioperative hypotension and comparing vasopressin receptor agonists with norepinephrine. The risk of bias was assessed by the Cochrane risk of bias tool for randomized trials (RoB-2). Thirteen (N = 719) RCTs were included, of which 8 (n = 585) enrolled patients undergoing cardiac surgery. Five trials compared norepinephrine with vasopressin, 4 trials with terlipressin, 1 trial with ornipressin, and the other 3 trials used vasopressin as adjuvant therapy. There was no significant difference in all-cause mortality. Among patients with vasoplegic shock after cardiac surgery, vasopressin was associated with significantly lower intensive care unit (N = 385; 2 trials; mean 100.8 v 175.2 hours, p < 0.005; median 120 [IQR 96-168] v 144 [96-216] hours, p = 0.007) and hospital lengths of stay, as well as fewer cases of acute kidney injury and atrial fibrillation compared with norepinephrine. One trial also found that terlipressin was associated with a significantly lower incidence of acute kidney injury versus norepinephrine overall. Vasopressin and norepinephrine restored mean arterial blood pressure with no significant differences; however, the use of vasopressin with norepinephrine was associated with significantly higher mean arterial blood pressure versus norepinephrine alone. Further high-quality trials are needed to determine pooled treatment effects, especially among noncardiac surgical patients and those treated with vasopressin analogs.

Obesity and Extracorporeal Membrane Oxygenation (ECMO): Analysis of Outcomes.

Traditionally, patients with obesity have been deemed ineligible for extracorporeal life support (ELS) therapies such as extracorporeal membrane oxygenation (ECMO), given the association of obesity with chronic health conditions that contribute to increased morbidity and mortality. Nevertheless, a growing body of literature suggests the feasibility, efficacy, and safety of ECMO in the obese population. This review provides an in-depth analysis of the current literature assessing the effects of obesity on outcomes among patients supported with ECMO (venovenous [VV] ECMO in noncoronavirus disease 2019 and coronavirus disease 2019 acute respiratory distress syndrome, venoarterial [VA] ECMO, and combined VV and VA ECMO), offer a possible explanation of the current findings on the basis of the obesity paradox phenomenon, provides a framework for future studies addressing the use of ELS therapies in the obese patient population, and provides guidance from the literature for many of the challenges related to initiating, maintaining, and weaning ELS therapy in patients with obesity.

Remimazolam in Cardiac Anesthesia: Analysis of Recent Data.

Interest in remimazolam has surged in recent years, thanks to its advantageous pharmacologic profile. This ultra-short-acting benzodiazepine is noted for its rapid onset and termination of action, organ-independent elimination, availability of a reversal agent, and excellent hemodynamic stability. Although the use of remimazolam has been explored in various anesthesia settings and procedures, data on its application in cardiovascular anesthesia and catheterization laboratory procedures remain limited. This review evaluates the latest literature to assess remimazolam's role in cardiovascular anesthesia across different settings and procedures. The analysis shows that remimazolam offers anesthesia without significant hemodynamic instability and a reduced need for vasopressors, with an incidence of perioperative adverse events comparable to that of other agents. These findings are relevant for both the induction and maintenance of general anesthesia in catheterization laboratory procedures and general anesthesia in elective cardiac surgery. Although further research is needed to fully understand remimazolam's role in cardiovascular anesthesia, its favorable hemodynamic and safety profile suggests that it is a promising option for cardiac anesthesiologists in both the catheterization laboratory and the operating room.

HeartMate 3: Analysis of Outcomes and Future Directions.

Heart failure (HF) remains a public health concern affecting millions of individuals worldwide. Despite recent advances in device-related therapies, the prognosis for patients with chronic HF remains poor with significant long-term risk of morbidity and mortality. Left ventricular assist devices (LVADs) have transformed the landscape of advanced HF management, offering circulatory support as destination therapy or as a bridge for heart transplantation. Among the latest generation of LVADs, the HeartMate 3 has gained popularity due to improved clinical outcomes and lower risk of serious adverse events when compared with previous similar devices. The ELEVATE (Evaluating the HeartMate 3 with Full MagLev Technology in a Post-Market Approval Setting) Registry and the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial represent landmark investigations into the performance and comparative effectiveness of the HeartMate 3 LVAD. This review provides a comprehensive synthesis of the safety and efficacy of the 2-year and 5-year HeartMate LVAD outcomes, highlighting key findings, methodological considerations, implications for clinical practice, and future directions.

Should Obesity Be an Exclusion Criterion for Extracorporeal Membrane Oxygenation Support? A Scoping Review.

Obesity is often considered a contraindication to extracorporeal membrane oxygenation (ECMO) candidacy due to technical challenges with vascular access, higher cardiac output requirements, and known associations between obesity and overall increased morbidity and mortality due to chronic health conditions. However, a growing body of literature suggests that ECMO may be as safe and efficacious in both obese and nonobese patients. This scoping review provides a synthesis of the available literature on the outcomes of obese patients supported with (1) venovenous (VV)-ECMO in acute respiratory distress syndrome (ARDS) not due to coronavirus disease 2019 (COVID-19), (2) VV-ECMO in ARDS due to COVID-19, (3) venoarterial (VA)-ECMO for all indications, and (4) studies combining data of patients supported with VA- and VV-ECMO. A librarian-assisted search was performed using 4 primary electronic medical databases (PubMed, Web of Science, Excerpta Medica database [Embase], and Cochrane Library) from January 2003 to March 2023. Articles that reported outcomes of obese patients requiring ECMO support were included. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. A total of 354 publications were imported for screening on titles and abstracts, and 30 studies were selected for full-text review. A total of 26 publications met the inclusion criteria: 7 on VV-ECMO support in non-COVID-19 ARDS patients, 6 on ECMO in COVID-19 ARDS patients, 8 in patients supported with VA-ECMO, and 5 combining both VA- and VV-ECMO data. Although the included studies are limited to retrospective analyses and display a heterogeneity in definitions of obesity and comparison groups, the currently available literature suggests that outcomes and complications of ECMO therapy are equivalent in obese patients as compared to nonobese patients. Hence, obesity as measured by body mass index alone should not be considered an exclusion criterion in the decision to initiate ECMO.

Coagulation Tests and Bleeding Classification After Cardiopulmonary Bypass: A Prospective Study.

OBJECTIVE: No recent prospective studies have analyzed the accuracy of standard coagulation tests and thromboelastography (TEG) to identify patients with excessive microvascular bleeding following cardiopulmonary bypass (CPB). The aim of this study was to assess the value of coagulation profile tests, as well as TEG, for the classification of microvascular bleeding after CPB. DESIGN: A prospective observational study. SETTING: At a single-center academic hospital. PARTICIPANTS: Patients ≥18 years of age undergoing elective cardiac surgery. INTERVENTIONS: Qualitative assessment of microvascular bleeding post-CPB (surgeon and anesthesiologist consensus) and the association with coagulation profile tests and TEG values. MEASUREMENTS AND MAIN RESULTS: A total of 816 patients were included in the study-358 (44%) bleeders and 458 (56%) nonbleeders. Accuracy, sensitivity, and specificity for the coagulation profile tests and TEG values ranged from 45% to 72%. The predictive utility was similar across tests, with prothrombin time (PT) (62% accuracy, 51% sensitivity, 70% specificity), international normalized ratio (INR) (62% accuracy, 48% sensitivity, 72% specificity), and platelet count (62% accuracy, 62% sensitivity, 61% specificity) displaying the highest performance. Secondary outcomes were worse in bleeders versus nonbleeders, including higher chest tube drainage, total blood loss, transfusion of red blood cells, reoperation rates (p < 0.001, respectively), readmission within 30 days (p = 0.007), and hospital mortality (p = 0.021). CONCLUSIONS: Standard coagulation tests and individual components of TEG in isolation agree poorly with the visual classification of microvascular bleeding after CPB. The PT-INR and platelet count performed best but had low accuracy. Further work is warranted to identify better testing strategies to guide perioperative transfusion decisions in cardiac surgical patients.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Sex-Specific Associations Between Preoperative Anemia and Postoperative Clinical Outcomes in Patients Undergoing Cardiac Surgery.

BACKGROUND: Preoperative anemia is common in cardiac surgery, yet there were limited data describing the role of sex in the associations between anemia and clinical outcomes. Understanding these relationships may guide preoperative optimization efforts. METHODS: This is an observational cohort study of adults undergoing isolated coronary artery bypass grafting or single- or double-valve surgery from 2008 to 2018 at a large tertiary medical center. Multivariable regression assessed the associations between preoperative hemoglobin concentrations and a primary outcome of postoperative acute kidney injury (AKI) and secondary outcomes of perioperative red blood cell (RBC) transfusion, reoperation, vascular complications (ie, stroke, pulmonary embolism, and myocardial infarction), and hospital length of stay (LOS). Each outcome was a single regression model, using interaction terms to assess sex-specific associations between hemoglobin and outcome. RESULTS: A total of 4117 patients were included (57% men). Linear splines with sex-specific knots (13 g/dL in women and 14 g/dL in men) provided the best overall fit for preoperative hemoglobin and outcome relationships. In women, each 1 g/dL decrease in hemoglobin <13 g/dL was associated with increased odds of AKI (odds ratio = 1.49; 95% confidence interval [CI], [1.23-1.81]; P < .001), and there was no significant association between hemoglobin per 1 g/dL >13 g/dL and AKI (0.90 [0.56-1.45]; P = .67). The association between hemoglobin and AKI in men did not meet statistical significance (1.10 [0.99-1.22]; P = .076, per 1 g/dL decrease <14 g/dL; 1.00 [0.79-1.26]; P = .98 for hemoglobin per 1 g/dL >14 g/dL). In women, lower preoperative hemoglobin (per 1 g/dL decrease <13 g/dL) was associated with increased odds of RBC transfusion (2.90 [2.33-3.60]; P < .001), reoperation (1.27 [1.11-1.45]; P < .001) and a longer hospital LOS (multiplicative increase in geometric mean 1.05 [1.03-1.07]; P < .001). In men, preoperative hemoglobin (per 1 g/dL decrease <14 g/dL) was associated with increased odds of perioperative RBCs (2.56 [2.27-2.88]; P < .001) and longer hospital LOS (multiplicative increase in geometric mean 1.02 [1.01-1.04] days; P < .001) but not reoperation (0.94 [0.85-1.04]; P = .256). Preoperative hemoglobin per 1 g/dL >13 g/dL in women and 14 g/dL in men were associated with lower odds of RBCs transfusion (0.57 [0.47-0.69]; P < .001 and 0.74 [0.60-0.91]; P = .005, respectively). CONCLUSIONS: Preoperative anemia was associated with inferior clinical outcomes after cardiac surgery. The associations between hemoglobin and outcomes were distinct for women and men, with different spline knot points identified (13 and 14 g/dL, respectively). Clinicians should consider data-driven approaches to determine preoperative hemoglobin values associated with increasing risk for adverse perioperative outcomes across sexes.

Convalescent Plasma for Infectious Diseases: Historical Framework and Use in COVID-19.

Convalescent plasma has emerged as a promising therapeutic agent for patients with coronavirus disease 2019 (COVID-19), has received emergency use authorization, and is being widely used during the COVID-19 pandemic. Passive antibody therapy via plasma or serum has been successfully used to treat infectious diseases for more than a century. Passive antibody administration is based on the presumption that convalescent plasma or serum contains therapeutic antibodies that can be passively transferred to the plasma recipient. There are numerous examples in which convalescent plasma has been used successfully as post-exposure prophylaxis and treatment of infectious diseases, including previous coronavirus outbreaks. In the context of the COVID-19 pandemic, convalescent plasma was demonstrated to be safe and potentially effective among patients infected with COVID-19. This review provides an overview of the historical uses of convalescent plasma therapy, summarizes current evidence for convalescent plasma use for COVID-19, and highlights future antibody therapies.

Sex differences in paediatric airway anatomy.

NEW FINDINGS: What is the central question of this study? Are sex difference in the central airways present in healthy paediatric patients? What is the main finding and its importance? In patients ≤12 years we found no sex differences in central airway luminal area. After 14 years, the males had significantly larger central airway luminal areas than the females. The sex differences were minimized, but preserved when correcting for height. Luminal area is the main determinant of airway resistance and our finding could help explain sex differences in pulmonary system limitations to exercise in paediatric patients. ABSTRACT: Cross-sectional airway area is the main determinant of resistance to airflow in the respiratory system. In paediatric patients (<18 years), previous evidence for sex differences in cross-sectional airway area was limited to patients with history of pulmonary disease or cadaveric studies with small numbers of subjects. These studies either only report tracheal data and do not include a range of ages or correct for height. Therefore, we sought to assess sex differences in airway luminal area utilizing paediatric patients of varying ages and no history of respiratory disease. Using three-dimensional reconstructions from high-resolution computed tomography scans, we retrospectively assessed the cross-sectional airway area in healthy paediatric females (n = 97) and males (n = 128) over a range of ages (1-17 years). The areas of the trachea, left main bronchus, left upper lobe, left lower lobe, right main bronchus, intermediate bronchus and right upper lobe were measured at three discrete points by a blinded investigator. No differences between the sexes were noted in the cross-sectional areas of the youngest (ages 1-12 years) patients (P > 0.05). However, in patients ≥14 years the cross-sectional areas were larger in the males compared to females in most airway sites. For instance, the cross-sectional size of the trachea was 25% (218 ± 44 vs. 163 ± 24 mm2 , P < 0.01) larger in males vs. females among ages 13-17 years. When accounting for height, these sex differences in airway areas were attenuated, but persisted. Our results indicate that sex differences in paediatric airway cross-sectional area manifest after age ≥14 years and are independent of height.

Multidisciplinary Perioperative Management of Pulmonary Arterial Hypertension in Patients Undergoing Noncardiac Surgery.

OBJECTIVES: To describe the effect of implementing a contemporary perioperative pulmonary hypertension (PH)-targeted protocol in patients with pulmonary arterial hypertension (PAH) undergoing noncardiac surgery (NCS). METHODS: The data of consecutive patients with PAH diagnosed by right heart catheterization who underwent NCS between January 1, 2006 and February 9, 2016 were reviewed. Patient demographics, etiology of PAH, clinical features, diagnostic data, utilization of PH-specific medications, and trend of perioperative complications rate were recorded during the study period. RESULTS: In the base cohort of 375 patients, 37 had NCS. The mean age at surgery was 62 years. Most patients were women (78%) classified in group 1 PAH. At the time of the surgery, 86% were New York Heart Association functional class III/IV and 97% had American Society of Anesthesiologists classifications 3 and 4. A larger proportion of patients displayed lower PAH risk scores between 2006 and 2011 (P = 0.045). Conversely, a higher percentage of patients exhibited moderately high to very high PAH risk scores between 2012 and 2016 (P = 0.003). Perioperative and anesthetic-related morbidity was 27%, and no difference was observed between either period (P = 0.944). Most of the complications (70%) were related to general anesthesia. Two deaths (5%) occurred in our study group, both during the 2006-2011 period. CONCLUSIONS: The combination of a multidisciplinary perioperative approach, utilization of novel pulmonary vascular disease-targeted therapy, adequate perioperative optimization, and thoughtful selection of anesthetic technique seems to be a potential strategy to at least maintain similar perioperative outcomes among higher- and lower-risk patients with PAH undergoing NCS.

Pain in the Elderly.

Pain management in the elderly has increasingly become problematic in the USA as the aged population grows. The proportion of the population over 65 continues to climb and may eclipse 20 % in the next decade. In order to effectively diagnosis and treat these patients, a proper history and physical exam remain essential; pain assessment scales such as the Verbal Descriptor Scales (VDS), the Numerical Rating Scales (NRS), and the Visual Analogue Scales (VAS) often but not always prove beneficial. The conditions most frequently afflicting this population include osteoarthritis, diabetic neuropathy, post-herpetic neuralgia, and lower back pain which include spondylosis and radiculopathies. While the normal aging process does not necessarily guarantee symptoms of chronic pain, elderly individuals are far more likely to develop these painful conditions than their younger counterparts. There are many effective treatment modalities available as potential therapeutic interventions for elderly patients, including but not limited to analgesics such as NSAIDs and opioids, as well as multiple interventional pain techniques. This review will discuss chronic pain in the elderly population, including epidemiology, diagnostic tools, the multitude of co-morbidities, and common treatment modalities currently available to physicians.

Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19: a retrospective case-control study.

Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10-30% of patients with acute COVID-19 infection, symptoms persist for more than 4 wk (referred to as post-acute sequelae of COVID 19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate whether luminal area of large conducting airways is different between patients with PASC and COVID-19 and healthy controls. In this retrospective case-control study, 75 patients with PASC (48 females) were age-, height-, and sex-matched to 75 patients with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi. Kruskal-Wallis H test was used to compare measurements between the three groups, as appropriate. Airway luminal areas between COVID-19 and PASC groups were not different (all, P > 0.66). There were no group differences in airway luminal area (PASC vs. control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12-39% larger among patients with PASC than in controls (all, P < 0.05). Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared with healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for reversal of changes.NEW & NOTEWORTHY Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19.

Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 ("vax-plasma"). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% (P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization.IMPORTANCEAs SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

Contemporary Perioperative Management of Direct Oral Anticoagulants.

Direct oral anticoagulants (DOACs) have rapidly emerged as popular alternatives to warfarin in the setting of nonvalvular atrial fibrillation, prevention and treatment of venous thromboembolism, and secondary prevention of arterial thrombosis. It is now estimated that more patients in the United States take DOACs than warfarin for approved indications. Studies to date have shown that these drugs are similarly efficacious with perhaps a lower bleeding risk than warfarin. The purpose of this review is to provide insight into the currently available DOACs and discuss the management and reversal strategies for patients in the perioperative period.